Umbrella Trial Testing Integrative Subtype-Targeted Therapeutics in HR+ /HER2-Negative Breast Cancer


Trial ID: NCT05101564


The purpose of this study is to learn if adding a new drug that is targeted at a specific genetic change found in some breast tumors pre-operatively will slow the growth of the tumor more than standard anti-hormone therapy used to treat this type of breast cancer. Different therapies are being tested based on the specific gene changes in the tumor. Not every tumor will have a gene change that is being studied.

Official Title

An Umbrella, Randomized, Controlled, Pre-Operative Trial Testing Integrative Subtype-Targeted Therapeutics in Hormone Receptor-Positive, HER2-Negative Breast Cancer

Stanford Investigator(s)

Jennifer Caswell-Jin
Jennifer Caswell-Jin

Assistant Professor of Medicine (Oncology)


Inclusion Criteria:

   - Pre-Screening Phase

   - Biopsy-proven ER-positive, HER2-negative breast cancer. ER-positivity and
   PR-positivity are defined as ≥1% cells staining positive by immunohistochemistry.
   HER2-negativity is defined by IHC or FISH, per ASCO-CAP 2018 guidelines. Breast tumor
   must be intact and tumor size must be ≥ 1 cm as measured by ultrasound, mammogram,
   MRI, or clinical exam. If tumor is locally recurrent, it must be in the breast (not
   skin, node, or chest wall recurrence). Ki67 may or may not have been done locally but
   if done locally, must be ≥ 5%. Any nodal status is allowed, as M0 or M1 disease.

   - Women or men, age ≥ 18 years old.

   - Performance status 0 to 1 (by Eastern Cooperative Oncology Group [ECOG] scale).

   - Ability to understand and the willingness to sign a written informed consent document.

Treatment Phase

   - Breast tumor classifies as relevant integrative subtype per tumor sequencing performed
   and analyzed by central laboratory.

   - Breast tumor Ki67 score ≥ 10% as assessed by central laboratory.

   - Each investigational agent specific inclusion criteria can be found in the
   agent-specific appendix

Exclusion Criteria:

   - Pregnant woman, as confirmed by positive serum hCG test prior to initiating study
   treatment. Nursing (lactating) woman also not allowed.

   - Prior breast cancer-directed therapy (surgery, radiation, chemotherapy, or endocrine
   therapy) is not allowed, with the exception of people with in-breast recurrences.
   People with in-breast recurrences cannot have had breast cancer-directed therapy
   (radiation, chemotherapy, or endocrine therapy; surgery is acceptable) within the 6
   months prior to signing the pre-screening consent. Pre-endocrine therapy for breast
   cancer risk reduction is allowed.

   - Known hypersensitivity to study agent (IP) or standard endocrine therapy drug, or to
   any of the excipients of study agent (IP) or standard endocrine therapy drug.

   - Each study agent specific exclusion criteria can be found in the agent-specific


drug: Alpelisib

drug: Tamoxifen

drug: Zotatifin

drug: Fulvestrant


Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Allison Zhang